Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19
Authors: Patricia Fanlo, Borja del Carmelo Gracia-Tello, Eva Fonseca Aizpuru, Jorge Álvarez-Troncoso, Andrés Gonzalez, Sergio Prieto-González, Mayka Freire, Ana Belén Argibay, Lucio Pallarés, José Antonio Todolí, Mercedes Pérez, Segundo Buján-Rivas, Berta Ibáñez, Rubén Arnáez, Elisa Huarte, Julio Sanchez, Eva Zabalza, Ruth Garcia-Rey, Maria Gonzalo, Laura Diez-Galán, Marisa de la Rica-Escuín, Luis Martinez-Lostao, Adela Marín Ballvé, María Luisa Taboada-Martínez, Rubén Pampín-Sánchez, Cristina Helguera-Amézua, Rosa Fernández-Madera-Martínez, Estela García-Coya, Ana María Álvarez-Suarez, Ángel Robles, Ana Noblejas, Clara Soto, Elena Martínez, Francisco Arnalich, Coral Arévalo, Angélica  López-Rodríguez, Pilar Cobeta, Fernando Hidalgo, Sergio Diz, Paula González, Nuria Bara, Martin Fabregate, Judith Jiménez, Svetlana Zhilina, Martina Pellicer-Ariño, Olga Rodríguez -Núñez, Joan Ribot -Grabalosa, Míriam Costafreda-Mas, Adrián Tomé-Pérez, Teresa Hospital-Vidal, Andrea Ladino-Vázquez, Alma Morancho-Sesé, Adelaido Salazar-Rustarazo, Cristina Gabara-Xancó, Arturo Gonzalez -Quintela, Bernardo Sopeña, Rosario Alende -Sixto, Helena Esteban, Nuria Rodriguez-Nuñez, Ariadna Helena Andrade-Piña, Maria Ángeles Sanchidrian-Chapinal, Pablo Varela, Manuel Taboada, Brenda Maure-Noia, Ana López-Domínguez, Carmen Filloy-Mato, Beatriz Gimena-Reyes, Marisol Samartín-Ucha, Caritina Vázquez-Triñanes, Julian Fernández-Martín, Adolfo Paradela-Carreiro, Ana María Regueira-Arcay, Eva Esteban-Marcos, Luisa Martin-Pena, Juan Antonio Fernández-Navarro, Noelia Abdilla-Bonias, Jaume Mestre-Torres, Joana Rita Marques-Soares, Josep Pardos-Gea
Journal: JAMA Network Open (2023)

COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear.To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation.The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, ≥5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021.Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously.The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-to-treat basis.A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99).In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia.ClinicalTrials.gov Identifier: NCT04443881.